title: Metal-polybenzimidazole complexes as a nonviral gene carrier: effects of the DNA affinity on gene delivery.
abstract: The metal complex-based carriers are emerging likely as a new type of gene-delivery systems prone to systematic structural alteration and chemical tailoring. In our work, the DNA affinity of metal complexes with polybenzimidazoles was found to be one of the determinants that can regulate expression of the transgenes. Here, the correlations between the DNA affinity and transfection efficacy were explored by characterizing gene-delivering properties of a series of Co(2+)- and Ca(2+)-polybenzimidazole complexes. The binding equilibrium constants (Kobs) of the divalent metal complexes to DNA, which is considered as a measure of the DNA affinity of metal complexes, were evaluated by isothermal titration calorimetry (ITC) and UV-visible absorption titration. The properties of DNA condensates formed with the metal complexes including sizes, ζ potential and morphology were observed to be altered with Kobs values. The monodispersed spherical condensates were found only for the Ca(2+) complexes whose DNA affinity is weaker than that of the Co(2+) complexes. However, the cell internalization examination indicated that cell uptake of the DNA condensates is independent of homogeneity in their sizes and morphology. The comparison of transgene expression showed that that the Ca(2+) complex-mediated transfection has higher efficiency than the Co(2+) complexes under the conditions tested, and the transfection efficacy cannot be correlated with the cell uptake of DNA condensates. Moreover, the Ca(2+) complexes and their DNA condensates had lower cytotoxicity than the Co(2+) complexes. Thus, the DNA affinity should be one of the factors to be capable of regulating the gene-delivering property of metal complexes.
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, and School of Chemistry, Central China Normal University, Wuhan 430079, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Huang
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Dong
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Xianggao
authors.initials: X
authors.lastname: Meng
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.forename: Changlin
authors.initials: C
authors.lastname: Liu
mesh_terms: D001562:Benzimidazoles / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry*; D003035:Cobalt / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014162:Transfection / Q000379:methods*
chemical_list: D001562:Benzimidazoles; D011108:Polymers; D003035:Cobalt; D004247:DNA; C031000:benzimidazole; D002118:Calcium
keywords: Co(2+)/Ca(2+) complex; Condensation; Cytotoxicity; DNA affinity; Transfection efficacy